The candidate, Ronda Moore, DVM, has ten years of professional experience in clinical veterinary medicine and veterinary pathology and has specific interests in gastrointestinal disease. Her extended goal is to become an independent investigator in gastrointestinal disease of animals which have relevance to human disease counterparts. The candidate's short-term goal is to acquire research expertise essential for the study of the intestinal mucosal barrier in evolving and restitution disease states of animals. During the initial phase of this proposal a model of intestinal injury in the guinea pig induced by Ca++ depletion will provide a data base relating to structural and functional alterations in the mucosal barrier during and following recovery of intestinal injury and will allow the candidate to gain technical expertise in a variety of techniques used to study intestinal barrier function. Techniques utilized during the initial three years will include: light and electron microscopy, ultrastructural tracer molecule studies, freeze-fracture and in vitro electrophysiological techniques. During the final phase of this proposal, the candidate will apply the technical expertise acquired during the initial phase to barrier function and restitution in a natural form of intestinal mucosal injury, viral enteritis. In this final phase the TGE virus infected piglet will be used as the animal model of viral enteritis. The research efforts of the sponsor, Dr. James Madara, Associate Professor of Pathology, Havard Medical School, are focused on structure-function correlates in normal intestinal mucosa and in the regulation of physiological permeability responses. His laboratory utilizes all the techniques listed above and also interacts and collaborates with other laboratories located in the Harvard Medical School area which study digestive diseases. In addition, Dr. Muthiah Daniel an experienced veterinary virologist will provide the needed support in the area of virology during the TGE phase of this project. These studies conducted in this environment should not only yield significant insights into mucosal barrier structure-function in general and into intestinal barrier function in TGE in particular but will also serve to provide the candidate with the indepth research experience which will allow her to pursue her goals as an independent investigator in the field of gastrointestinal disease of animals and man.